PMID- 22895785
OWN - NLM
STAT- MEDLINE
DCOM- 20131231
LR  - 20220317
IS  - 1791-2423 (Electronic)
IS  - 1019-6439 (Linking)
VI  - 41
IP  - 4
DP  - 2012 Oct
TI  - The mTOR inhibitor RAD001 augments radiation-induced growth inhibition in a 
      hepatocellular carcinoma cell line by increasing autophagy.
PG  - 1381-6
LID - 10.3892/ijo.2012.1583 [doi]
AB  - Treatment of hepatocellular carcinoma (HCC) is a major concern for physicians as 
      its response to chemotherapy and radiotherapy remains generally poor, due, in 
      part, to intrinsic resistance to either form of treatment. We previously reported 
      that an irradiation with fast neutrons, which are high-linear energy transfer 
      (LET) particles, massively induced autophagic cell death in the human HCC SK-Hep1 
      cell line. In the present study, we tested the capacity of the mammalian target 
      of rapamycin (mTOR) inhibitor RAD001 to augment the cytotoxicity of low and 
      high-LET radiation in these cells. As mTOR is a key component in a series of 
      pathways involved in tumor growth and development, it represents a potential 
      molecular target for cancer treatment. Results indicate that RAD001, at 
      clinically relevant nanomolar concentrations, enhances the efficacy of both high- 
      and low-LET radiation in SK-Hep1 cells, and that the induction of autophagy may 
      account for this effect. However, fast neutrons were found to be more efficient 
      at reducing tumor cell growth than low-LET radiation.
FAU - Altmeyer, Anais
AU  - Altmeyer A
AD  - EA 3430, University of Strasbourg, Centre Paul Strauss, Strasbourg, France.
FAU - Josset, Elodie
AU  - Josset E
FAU - Denis, Jean-Marc
AU  - Denis JM
FAU - Gueulette, John
AU  - Gueulette J
FAU - Slabbert, Jakobus
AU  - Slabbert J
FAU - Mutter, Didier
AU  - Mutter D
FAU - Noel, Georges
AU  - Noel G
FAU - Bischoff, Pierre
AU  - Bischoff P
LA  - eng
PT  - Journal Article
DEP - 20120807
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (Growth Inhibitors)
RN  - 0 (Radiation-Sensitizing Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Autophagy/drug effects/radiation effects
MH  - Carcinoma, Hepatocellular/pathology/*radiotherapy
MH  - Cell Line, Tumor/drug effects/radiation effects
MH  - Cell Proliferation/drug effects/*radiation effects
MH  - Everolimus
MH  - Growth Inhibitors/pharmacology
MH  - Humans
MH  - Linear Energy Transfer
MH  - Liver Neoplasms/pathology/*radiotherapy
MH  - Neutrons
MH  - Radiation-Sensitizing Agents/pharmacology
MH  - Sirolimus/analogs & derivatives/pharmacology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
EDAT- 2012/08/17 06:00
MHDA- 2014/01/01 06:00
CRDT- 2012/08/17 06:00
PHST- 2012/03/08 00:00 [received]
PHST- 2012/05/09 00:00 [accepted]
PHST- 2012/08/17 06:00 [entrez]
PHST- 2012/08/17 06:00 [pubmed]
PHST- 2014/01/01 06:00 [medline]
AID - 10.3892/ijo.2012.1583 [doi]
PST - ppublish
SO  - Int J Oncol. 2012 Oct;41(4):1381-6. doi: 10.3892/ijo.2012.1583. Epub 2012 Aug 7.